TFEB-mediated endolysosomal activity controls human hematopoietic stem cell fate
| Autor: | Alex Murison, Andy G.X. Zeng, Mathieu Lupien, Elvin Wagenblast, Veronique Voisin, Stephanie Z. Xie, Darrien Parris, Florin Schneiter, Kerstin B. Kaufmann, Weijia Wang, Laura García-Prat, Sabrina A. Smith, Kinam Gupta, Michelle C. Shoong, Gabriela Krivdova, Olga I. Gan, Jocelyn Chen, Kristele Pan, Timm Schroeder, Shin-Ichiro Takayanagi, Jessica McLeod, John E. Dick, Michelle Chan-Seng-Yue |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Lysosomes
endocytosis TFEB MYC long-term HSC self-renewal erythropoiesis myelopoiesis TfR1 anabolism Biology Endocytosis Genetics medicine Humans Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Catabolism Hematopoietic stem cell Cell Differentiation Cell Biology Hematopoietic Stem Cells Hematopoiesis Cell biology Haematopoiesis medicine.anatomical_structure Stem cell fate determination Molecular Medicine Myelopoiesis Stem cell Signal Transduction |
| Zdroj: | Cell Stem Cell, 28 (10) |
| ISSN: | 1934-5909 1875-9777 |
| DOI: | 10.3929/ethz-b-000510219 |
| Popis: | It is critical to understand how human quiescent long-term hematopoietic stem cells (LT-HSCs) sense demand from daily and stress-mediated cues and then transition into bioenergetically active progeny to differentiate and meet these cellular needs. However, the demand-adapted regulatory circuits of these early steps of hematopoiesis are largely unknown. Here we show that lysosomes, sophisticated nutrient-sensing and signaling centers, are regulated dichotomously by transcription factor EB (TFEB) and MYC to balance catabolic and anabolic processes required for activating LT-HSCs and guiding their lineage fate. TFEB-mediated induction of the endolysosomal pathway causes membrane receptor degradation, limiting LT-HSC metabolic and mitogenic activation, promoting quiescence and self-renewal, and governing erythroid-myeloid commitment. In contrast, MYC engages biosynthetic processes while repressing lysosomal catabolism, driving LT-HSC activation. Our study identifies TFEB-mediated control of lysosomal activity as a central regulatory hub for proper and coordinated stem cell fate determination. Cell Stem Cell, 28 (10) ISSN:1934-5909 ISSN:1875-9777 |
| Databáze: | OpenAIRE |
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